Insiders\u27 perspectives on project based learning: A comparison of US and Israeli approaches

High school students and teachers in two countries (US and Israel) were interviewed to ascertain their perspectives about their Project Based Learning (PBL) experiences. Perspectives were evaluated to determine to what degree PBL approaches were based on the eight essential elements of PBL and whether PBL courses contributed effectively to workplace preparedness. Differences between teachers and students and between countries were identified. Results revealed that PBL programs incorporating the eight essential elements are more effective in preparing students to enter today’s work environment. Students perceive stronger benefits from their PBL experiences than teachers perceive. Additionally, the perspectives of Israeli teachers and students were more similar to each other than the perspectives of US teachers and students

Multireference Alignment is Easier with an Aperiodic Translation Distribution

In the multireference alignment model, a signal is observed by the action of a random circular translation and the addition of Gaussian noise. The goal is to recover the signal's orbit by accessing multiple independent observations. Of particular interest is the sample complexity, i.e., the number of observations/samples needed in terms of the signal-to-noise ratio (the signal energy divided by the noise variance) in order to drive the mean-square error (MSE) to zero. Previous work showed that if the translations are drawn from the uniform distribution, then, in the low SNR regime, the sample complexity of the problem scales as $\omega(1/\text{SNR}^3)$. In this work, using a generalization of the Chapman--Robbins bound for orbits and expansions of the $\chi^2$ divergence at low SNR, we show that in the same regime the sample complexity for any aperiodic translation distribution scales as $\omega(1/\text{SNR}^2)$. This rate is achieved by a simple spectral algorithm. We propose two additional algorithms based on non-convex optimization and expectation-maximization. We also draw a connection between the multireference alignment problem and the spiked covariance model

Reversible disruption of XPO1-mediated nuclear export inhibits respiratory syncytial virus (RSV) replication

Respiratory syncytial virus (RSV) is the primary cause of serious lower respiratory tract disease in infants, young children, the elderly and immunocompromised individuals. Therapy for RSV infections is limited to high risk infants and there are no safe and efficacious vaccines. Matrix (M) protein is a major RSV structural protein with a key role in virus assembly. Interestingly, M is localised to the nucleus early in infection and its export into the cytoplasm by the nuclear exporter, exportin-1 (XPO1) is essential for RSV assembly. We have shown previously that chemical inhibition of XPO1 function results in reduced RSV replication. In this study, we have investigated the anti-RSV efficacy of Selective Inhibitor of Nuclear Export (SINE) compounds, KPT-335 and KPT-185. Our data shows that therapeutic administration of the SINE compounds results in reduced RSV titre in human respiratory epithelial cell culture. Within 24 h of treatment, RSV replication and XPO1 expression was reduced, M protein was partially retained in the nucleus, and cell cycle progression was delayed. Notably, the effect of SINE compounds was reversible within 24 h after their removal. Our data show that reversible inhibition of XPO1 can disrupt RSV replication by affecting downstream pathways regulated by the nuclear exporter

Selinexor, a novel selective inhibitor of nuclear export, reduces SARS-CoV-2 infection and protects the respiratory system in vivo

The novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the recent global pandemic. The nuclear export protein (XPO1) has a direct role in the export of SARS-CoV proteins including ORF3b, ORF9b, and nucleocapsid. Inhibition of XPO1 induces anti-inflammatory, anti-viral, and antioxidant pathways. Selinexor is an FDA-approved XPO1 inhibitor. Through bioinformatics analysis, we predicted nuclear export sequences in the ACE-2 protein and confirmed by in vitro testing that inhibition of XPO1 with selinexor induces nuclear localization of ACE-2. Administration of selinexor inhibited viral infection prophylactically as well as therapeutically in vitro. In a ferret model of COVID-19, selinexor treatment reduced viral load in the lungs and protected against tissue damage in the nasal turbinates and lungs in vivo. Our studies demonstrated that selinexor downregulated the pro-inflammatory cytokines IL-1β, IL-6, IL-10, IFN-γ, TNF-α, and GMCSF, commonly associated with the cytokine storm observed in COVID-19 patients. Our findings indicate that nuclear export is critical for SARS-CoV-2 infection and for COVID-19 pathology and suggest that inhibition of XPO1 by selinexor could be a viable anti-viral treatment option

An international survey of the diagnosis and management of Ménière's disease amongst otolaryngology consultants

oai:repository.canterbury.ac.uk:99745Ménière's Disease (MD) is a disease that may be difficult to diagnose and manage. Our UK survey showed variability in the practice of UK Otolaryngology consultants. We hence surveyed Otolaryngology consultants internationally, to assess their confidence levels in diagnosing MD, their use of the AAO-HNS guidelines and current diagnostic and treatment modalities. An online questionnaire was distributed internationally over four weeks. The questionnaire asked respondents to anonymously rank their confidence in diagnosing MD, identify the minimum investigations required to make a diagnosis, describe their use of the AAO-HNS criteria, share their preferred treatment modalities for acute attacks, and state their 1st and 2nd-line preventative treatment options. A total of 173 responses were collected with 77% of respondents reporting high levels of confidence in diagnosing MD. Most respondents stated the minimum tests required were "History, Otoscopy, Clinical Vestibular testing, and Pure Tone Audiometry" although some chose as few as 1 test. Regarding the use of the AAO-HNS criteria, responses ranged from "always" (20.2%) to "never" (22.5%). Cinnarizine was the first-line treatment for acute attacks followed by betahistine. Betahistine (30.1%) and dietary restrictions (28.3%) were recommended almost equally as first-line preventative measures. The most popular second-line measure was intratympanic steroids injection (30.1%). Our survey revealed disparities in the diagnosis of MD and its management, like the results of our previously conducted UK survey. This suggests the need for an international consensus regarding the diagnosis and subsequent management strategies for this disease

Otitis Media Practice During the COVID-19 Pandemic.

The global coronavirus disease-2019 (COVID-19) pandemic has changed the prevalence and management of many pediatric infectious diseases, including acute otitis media (AOM). Coronaviruses are a group of RNA viruses that cause respiratory tract infections in humans. Before the COVID-19 pandemic, coronavirus serotypes OC43, 229E, HKU1, and NL63 were infrequently detected in middle ear fluid (MEF) specimens and nasopharyngeal aspirates in children with AOM during the 1990s and 2000s and were associated with a mild course of the disease. At times when CoV was detected in OM cases, the overall viral load was relatively low. The new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen responsible for the eruption of the COVID-19 global pandemic. Following the pandemic declaration in many countries and by the World Health Organization in March 2020, preventive proactive measures were imposed to limit COVID-19. These included social distancing; lockdowns; closure of workplaces; kindergartens and schools; increased hygiene; use of antiseptics and alcohol-based gels; frequent temperature measurements and wearing masks. These measures were not the only ones taken, as hospitals and clinics tried to minimize treating non-urgent medical referrals such as OM, and elective surgical procedures were canceled, such as ventilating tube insertion (VTI). These changes and regulations altered the way OM is practiced during the COVID-19 pandemic. Advents in technology allowed a vast use of telemedicine technologies for OM, however, the accuracy of AOM diagnosis in those encounters was in doubt, and antibiotic prescription rates were still reported to be high. There was an overall decrease in AOM episodes and admissions rates and with high spontaneous resolution rates of MEF in children, and a reduction in VTI surgeries. Despite an initial fear regarding viral shedding during myringotomy, the procedure was shown to be safe. Special draping techniques for otologic surgery were suggested. Other aspects of OM practice included the presentation of adult patients with AOM who tested positive for SARS-2-CoV and its detection in MEF samples in living patients and in the mucosa of the middle ear and mastoid in post-mortem specimens

A Phase II Study of the Efficacy and Safety of Oral Selinexor in Recurrent Glioblastoma

PURPOSE: Selinexor is an oral selective inhibitor of exportin-1 (XPO1) with efficacy in various solid and hematological tumors. We assessed intra-tumoral penetration, safety, and efficacy of selinexor monotherapy for recurrent glioblastoma. PATIENTS AND METHODS: Seventy-six adults with Karnofsky Performance Status≥60 were enrolled. Patients undergoing cytoreductive surgery received up to three selinexor doses (twice weekly) pre-operatively (Arm A; N=8 patients). Patients not undergoing surgery received 50mg/m(2) (Arm B, N=24), or 60mg (Arm C, N=14) twice weekly, or 80mg once weekly (Arm D; N=30). Primary endpoint was six-month progression-free survival rate (PFS6). RESULTS: Median selinexor concentrations in resected tumors from patients receiving pre-surgical selinexor was 105.4nM (range 39.7-291nM). In Arms B, C, and D, respectively, the PFS6 was 10% (95%CI, 2.79-35.9), 7.7% (95%CI, 1.17-50.6), and 17% (95%CI, 7.78-38.3). Measurable reduction in tumor size was observed in 19 (28%) and RANO-response rate overall was 8.8% (Arm B, 8.3% (95%CI, 1.0-27.0); C:7.7% (95%CI, 0.2-36.0); D:10% (95%CI, 2.1-26.5)), with one complete and two durable partial responses in Arm D. Serious adverse events (AEs) occurred in 26 (34%) patients; one (1.3%) was fatal. The most common treatment-related AEs were fatigue (61%), nausea (59%), decreased appetite (43%) and thrombocytopenia (43%), and were manageable by supportive care and dose modification. Molecular studies identified a signature predictive of response (AUC=0.88). CONCLUSION: At 80mg weekly, single-agent selinexor induced responses and clinically relevant PFS6 with manageable side effects requiring dose reductions. Ongoing trials are evaluating safety and efficacy of selinexor in combination with other therapies for newly diagnosed or recurrent glioblastoma. TRIAL REGISTRATION: ClinicalTrials.gov, NCT0198634